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Clinical Trial Results:
A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of INCB001158 in Combination With Chemotherapy, in Subjects With Advanced or Metastatic Solid Tumors

Summary
EudraCT number	2017-002904-29
Trial protocol	GB BE
Global end of trial date	28 Nov 2022

Results information
Results version number	v1
This version publication date	26 Oct 2023
First version publication date	26 Oct 2023
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

INCB 01158-203

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Incyte Corporation

Sponsor organisation address

1801 Augustine Cutoff Drive, Wilmington, United States,

Public contact

Study Director, Incyte Corporation, 1 855-463-3463, medinfo@incyte.com

Scientific contact

Study Director, Incyte Corporation, 1 855-463-3463, medinfo@incyte.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Nov 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Nov 2022

Was the trial ended prematurely?

Main objective of the trial

Phase 1: To assess the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of INCB001158 in combination with chemotherapy Phase 2: To evaluate the objective response rate (ORR) of INCB001158 in combination with chemotherapy

Protection of trial subjects

This study was to be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the United States Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as International Conference on Harmonization Good Clinical Practice consolidated guidelines (E6) and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 17

Country: Number of subjects enrolled

United Kingdom: 37

Country: Number of subjects enrolled

United States: 95

Worldwide total number of subjects

149

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

This study was conducted at 11 study centers in the United States, the United Kingdom, and Belgium.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase 1: INCB001158 50 mg + mFOLFOX6

Arm description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 milligrams (mg) twice daily (BID) starting on Day 1 of each 28-day cycle. Participants also received intravenous modified FOLFOX6 (mFOLFOX6: oxaliplatin 85 mg/meters squared [m^2], leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Arm type

Experimental

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Investigational medicinal product name

leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection, Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

5-fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Phase 1: INCB001158 75 mg + mFOLFOX6

Arm description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Arm type

Experimental

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Investigational medicinal product name

leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection, Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

5-fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Phase 1: INCB001158 100 mg + mFOLFOX6

Arm description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Arm type

Experimental

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Investigational medicinal product name

leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection, Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

5-fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin

Arm description

Arm type

Experimental

Investigational medicinal product name

gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin

Arm description

Arm type

Experimental

Investigational medicinal product name

gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin

Arm description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and Day 8 of each 28-day cycle.

Arm type

Experimental

Investigational medicinal product name

gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 1: INCB001158 50 mg + Paclitaxel

Arm description

Arm type

Experimental

Investigational medicinal product name

paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1, 8, and 15 of each 28-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 1: INCB001158 75 mg + Paclitaxel

Arm description

Arm type

Experimental

Investigational medicinal product name

paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1, 8, and 15 of each 28-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 1: INCB001158 100 mg + Paclitaxel

Arm description

Arm type

Experimental

Investigational medicinal product name

paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1, 8, and 15 of each 28-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)

Arm description

In Phase 2, participants with microsatellite-stable-colorectal cancer (MSS-CRC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Arm type

Experimental

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Investigational medicinal product name

leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection, Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

5-fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Investigational medicinal product name

oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)

Arm description

In Phase 2, participants with biliary tract cancer (BTC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 25 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Arm type

Experimental

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Investigational medicinal product name

cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)

Arm description

In Phase 2, participants with ovarian cancer (OC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 750 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Arm type

Experimental

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Investigational medicinal product name

cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Investigational medicinal product name

gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1 and 8 of each 21-day cycle

Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)

Arm description

In Phase 2, participants with gastroesophageal cancer (GC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Arm type

Experimental

Investigational medicinal product name

paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1, 8, and 15 of each 28-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)

Arm description

In Phase 2, participants with endometrial cancer (EC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Arm type

Experimental

Investigational medicinal product name

paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1, 8, and 15 of each 28-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)

Arm description

In Phase 2, participants with ovarian cancer (OC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Arm type

Experimental

Investigational medicinal product name

paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

administered on Days 1, 8, and 15 of each 28-day cycle

Investigational medicinal product name

INCB001158

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Phase 1: administered orally BID as 25 mg or 100 mg tablets; Phase 2: administered orally in 28- or 21-day cycles depending on the chemotherapy regimen

Number of subjects in period 1	Phase 1: INCB001158 50 mg + mFOLFOX6	Phase 1: INCB001158 75 mg + mFOLFOX6	Phase 1: INCB001158 100 mg + mFOLFOX6	Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 50 mg + Paclitaxel	Phase 1: INCB001158 75 mg + Paclitaxel	Phase 1: INCB001158 100 mg + Paclitaxel	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)
Started	8	6	6	7	4	4	7	5	7	8	33	9	11	10	24
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	8	6	6	7	4	4	7	5	7	8	33	9	11	10	24
Adverse event, serious fatal	4	2	5	4	3	4	5	4	3	5	20	6	7	6	17
Consent withdrawn by subject	2	1	1	2	1	-	1	-	1	1	4	-	1	-	1
Progressive Disease	2	-	-	1	-	-	-	-	-	1	1	1	2	-	1
Captured as "Other" in Database	-	2	-	-	-	-	1	1	1	-	1	-	-	-	-
Study Terminated by Sponsor	-	1	-	-	-	-	-	-	1	-	7	2	1	4	4
Lost to follow-up	-	-	-	-	-	-	-	-	1	1	-	-	-	-	1

Baseline characteristics

Top of page

Reporting group title

Phase 1: INCB001158 50 mg + mFOLFOX6

Reporting group description

Reporting group title

Phase 1: INCB001158 75 mg + mFOLFOX6

Reporting group description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Reporting group title

Phase 1: INCB001158 100 mg + mFOLFOX6

Reporting group description

Reporting group title

Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin

Reporting group description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and Day 8 of each 28-day cycle.

Reporting group title

Phase 1: INCB001158 50 mg + Paclitaxel

Reporting group description

Reporting group title

Phase 1: INCB001158 75 mg + Paclitaxel

Reporting group description

Reporting group title

Phase 1: INCB001158 100 mg + Paclitaxel

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)

Reporting group description

Reporting group title

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)

Reporting group description

Reporting group title

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)

Reporting group description

Reporting group values	Phase 1: INCB001158 50 mg + mFOLFOX6	Phase 1: INCB001158 75 mg + mFOLFOX6	Phase 1: INCB001158 100 mg + mFOLFOX6	Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 50 mg + Paclitaxel	Phase 1: INCB001158 75 mg + Paclitaxel	Phase 1: INCB001158 100 mg + Paclitaxel	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)	Total
Number of subjects	8	6	6	7	4	4	7	5	7	8	33	9	11	10	24	149
Age categorical
Units: Subjects
Adults (18-64 years)	6	4	2	4	3	3	4	5	4	3	19	5	8	7	15	92
From 65-84 years	2	2	4	3	0	1	2	0	3	5	14	4	3	3	9	55
85 years and over	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	2
Age Continuous
Units: years
arithmetic mean (standard deviation)	56.4 ( 10.80 )	60.3 ( 9.93 )	65.2 ( 7.99 )	54.0 ( 18.93 )	64.5 ( 16.82 )	54.0 ( 15.64 )	62.0 ( 14.57 )	47.4 ( 10.29 )	61.4 ( 6.95 )	62.8 ( 11.26 )	59.3 ( 12.74 )	65.3 ( 8.87 )	58.8 ( 11.90 )	62.3 ( 9.29 )	60.6 ( 9.04 )	-
Sex: Female, Male
Units: participants
Female	3	4	3	3	2	3	5	4	5	3	21	9	4	10	24	103
Male	5	2	3	4	2	1	2	1	2	5	12	0	7	0	0	46
Race/Ethnicity, Customized
Units: Subjects
White	2	6	6	6	3	4	7	5	5	7	31	8	8	8	23	129
Black/African-American	2	0	0	0	0	0	0	0	1	1	1	0	0	1	0	6
Asian	1	0	0	0	1	0	0	0	1	0	0	0	2	1	1	7
American-Indian/Alaska Native	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
East Indian	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Not Provided/Specified	1	0	0	0	0	0	0	0	0	0	1	0	1	0	0	3
Black/Carribean	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Captured as Hispanic/Latino in Database	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	1	0	1	0	0	0	0	0	1	2	1	0	0	0	6
Not Hispanic or Latino	5	5	6	6	4	4	7	5	7	7	29	7	11	10	23	136
Unknown or Not Reported	3	0	0	0	0	0	0	0	0	0	2	1	0	0	1	7

End points

Top of page

Reporting group title

Phase 1: INCB001158 50 mg + mFOLFOX6

Reporting group description

Reporting group title

Phase 1: INCB001158 75 mg + mFOLFOX6

Reporting group description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Reporting group title

Phase 1: INCB001158 100 mg + mFOLFOX6

Reporting group description

Reporting group title

Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin

Reporting group description

Reporting group title

Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin

Reporting group description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and Day 8 of each 28-day cycle.

Reporting group title

Phase 1: INCB001158 50 mg + Paclitaxel

Reporting group description

Reporting group title

Phase 1: INCB001158 75 mg + Paclitaxel

Reporting group description

Reporting group title

Phase 1: INCB001158 100 mg + Paclitaxel

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)

Reporting group description

Reporting group title

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)

Reporting group description

Reporting group title

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)

Reporting group description

Reporting group title

Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)

Reporting group description

Subject analysis set title

Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 mg BID starting on Day 1 of each 28-day cycle. In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and MSS-CRC (Phase 2) also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. In Phases 1 and 2, participants with advanced or solid metastatic tumors (Phase 1) and MSS-CRC (Phase 2) also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6

Subject analysis set type

Full analysis

Subject analysis set description

In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and MSS-CRC (Phase 2) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 [bolus] and 2400 mg/m^2 [continuous infusion]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 50 mg+Gemcitabine+Cisplatin

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and Day 8 of each 28-day cycle. In Phase 2, participants with BTC received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 25 mg/m^2 on Day 1 and 8 of each 28-day cycle, and participants with OC received intravenous gemcitabine 750 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 75 mg+Gemcitabine+Cisplatin

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and Day 8 of each 28-day cycle. In Phase 2, participants with BTC received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 25 mg/m^2 on Day 1 and 8 of each 28-day cycle, and participants with OC received intravenous gemcitabine 750 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 100 mg+Gemcitabine+Cisplatin

Subject analysis set type

Full analysis

Subject analysis set description

In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and with BTC or OC (Phase 2) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. In Phase 1, participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and Day 8 of each 28-day cycle. In Phase 2, participants with BTC received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 25 mg/m^2 on Day 1 and 8 of each 28-day cycle, and participants with OC received intravenous gemcitabine 750 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 mg BID starting on Day 1 of each 28-day cycle. In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and with GC, EC, or OC (Phase 2) received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and with GC, EC, or OC (Phase 2) received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel

Subject analysis set type

Full analysis

Subject analysis set description

In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and GC, EC, or OC (Phase 2) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants with advanced or metastatic solid tumors (Phase 1) and with GC, EC, or OC (Phase 2) also received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Subject analysis set title

All Phase 1 Participants

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50, 75, or 100 mg BID plus intravenous modified FOLFOX6, intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2, or intravenous paclitaxel 80 mg/m^2.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 (Cohort B1)

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 2, for Pharmacokinetic (PK) analysis, participants with biliary tract cancer (BTC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 25 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Subject analysis set title

Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 (Cohort B1)

Subject analysis set type

Full analysis

Subject analysis set description

In Phase 2, for PK analysis, participants with biliary tract cancer (BTC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 25 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Primary: Phases 1 and 2: Number of participants with any treatment-emergent adverse event (TEAE)

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End point title

Phases 1 and 2: Number of participants with any treatment-emergent adverse event (TEAE) ^[1]

End point description

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

End point type

Primary

End point timeframe

up to 1385 days

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 50 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 75 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 100 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel	Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel	Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel
Number of subjects analysed	8	6	14	7	4	46	7	5	52
Units: participants	8	6	13	7	4	46	7	5	51

No statistical analyses for this end point

Primary: Phase 1: Number of participants with any dose-limiting toxicity (DLT)

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End point title

Phase 1: Number of participants with any dose-limiting toxicity (DLT) ^[2] ^[3]

End point description

A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria.

End point type

Primary

End point timeframe

up to Day 28

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 1: INCB001158 50 mg + mFOLFOX6	Phase 1: INCB001158 75 mg + mFOLFOX6	Phase 1: INCB001158 100 mg + mFOLFOX6	Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 50 mg + Paclitaxel	Phase 1: INCB001158 75 mg + Paclitaxel	Phase 1: INCB001158 100 mg + Paclitaxel
Number of subjects analysed	8	6	6	7	4	4	7	5	7
Units: participants	0	0	0	1	0	0	0	0	0

No statistical analyses for this end point

Primary: Recommended Phase 2 dose (RP2D) of INCB001158 when given in combination with each chemotherapy regimen

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End point title

Recommended Phase 2 dose (RP2D) of INCB001158 when given in combination with each chemotherapy regimen ^[4]

End point description

The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2.

End point type

Primary

End point timeframe

up to Day 580

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	All Phase 1 Participants
Number of subjects analysed	54
Units: milligrams	100

No statistical analyses for this end point

Primary: Phase 2: Objective Response Rate (ORR)

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End point title

Phase 2: Objective Response Rate (ORR) ^[5] ^[6]

End point description

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.

End point type

Primary

End point timeframe

up to 1385 days

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)
Number of subjects analysed	8	33	9	11	10	24
Units: percentage of participants
number (confidence interval 95%)	0.0 (0.0 to 36.9)	24.2 (11.1 to 42.3)	22.2 (2.8 to 60.0)	9.1 (0.2 to 41.3)	30.0 (6.7 to 65.2)	16.7 (4.7 to 37.4)

No statistical analyses for this end point

Secondary: Phase 1: ORR

Top of page

End point title

Phase 1: ORR ^[7]

End point description

ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, as determined by investigator assessment of radiographic disease as per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the Baseline sum diameters, no new lesions, and no progression of non-target lesions.

End point type

Secondary

End point timeframe

up to 580 days

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 1: INCB001158 50 mg + mFOLFOX6	Phase 1: INCB001158 75 mg + mFOLFOX6	Phase 1: INCB001158 100 mg + mFOLFOX6	Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin	Phase 1: INCB001158 50 mg + Paclitaxel	Phase 1: INCB001158 75 mg + Paclitaxel	Phase 1: INCB001158 100 mg + Paclitaxel
Number of subjects analysed	8	6	6	7	4	4	7	5	7
Units: percentage of participants
number (confidence interval 95%)	12.5 (0.3 to 52.7)	0.0 (0.0 to 45.9)	0.0 (0.0 to 45.9)	0.0 (0.0 to 41.0)	25.0 (0.6 to 80.6)	0.0 (0.0 to 60.2)	14.3 (0.4 to 57.9)	0.0 (0.0 to 52.2)	28.6 (3.7 to 71.0)

No statistical analyses for this end point

Secondary: Phases 1 and 2: Duration of Response

Top of page

End point title

Phases 1 and 2: Duration of Response

End point description

DOR was defined as the time from initial objective response (CR or PR) (as determined by investigator assessment of radiographic disease assessment per RECIST v1.1) until the earliest date of disease progression or death due to any cause, if it occurred sooner than disease progression. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. 9999=the upper limit of the confidence interval was not estimable because too few participants had disease progression or died. The Kaplan Meier estimation method on a sample size of less than 5 responders is not valid.

End point type

Secondary

End point timeframe

up to 368 days

Phase 1: INCB001158 50 mg + mFOLFOX6

Phase 1: INCB001158 75 mg + mFOLFOX6

Phase 1: INCB001158 100 mg + mFOLFOX6

Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 50 mg + Paclitaxel

Phase 1: INCB001158 75 mg + Paclitaxel

Phase 1: INCB001158 100 mg + Paclitaxel

Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)

Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)

Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)

Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)

Number of subjects analysed

0 ^[8]

0 ^[9]

0 ^[10]

0 ^[11]

0 ^[12]

0 ^[13]

0 ^[14]

0 ^[15]

0 ^[16]

0 ^[17]

0 ^[18]

0 ^[19]

0 ^[20]

0 ^[21]

Units: months

median (confidence interval 95%)

( to )

5.8 (4.1 to 9999)

( to )

Notes
[8] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[9] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[10] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[11] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[12] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[13] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[14] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[15] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[16] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[17] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[18] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[19] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[20] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).
[21] - Duration of response was analyzed in cohorts with >5 objective responders (CR or PR).

No statistical analyses for this end point

Secondary: Phases 1 and 2: Disease Control Rate

Top of page

End point title

Phases 1 and 2: Disease Control Rate

End point description

DCR was defined as the proportion of participants with an overall response of CR, PR, or stable disease (SD), as determined by investigator assessment of radiographic disease as per RECIST v1.1, for at least 8 weeks. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

End point type

Secondary

End point timeframe

up to 1385 days

Phase 1: INCB001158 50 mg + mFOLFOX6

Phase 1: INCB001158 75 mg + mFOLFOX6

Phase 1: INCB001158 100 mg + mFOLFOX6

Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 50 mg + Paclitaxel

Phase 1: INCB001158 75 mg + Paclitaxel

Phase 1: INCB001158 100 mg + Paclitaxel

Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)

Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)

Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)

Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)

Number of subjects analysed

Units: percentage of participants

number (confidence interval 95%)

62.5 (24.5 to 91.5)

83.3 (35.9 to 99.6)

16.7 (0.4 to 64.1)

57.1 (18.4 to 90.1)

75.0 (19.4 to 99.4)

100.0 (39.8 to 100.0)

42.9 (9.9 to 81.6)

60.0 (14.7 to 94.7)

85.7 (42.1 to 99.6)

100.0 (63.1 to 100.0)

66.7 (48.2 to 82.0)

88.9 (51.8 to 99.7)

54.5 (23.4 to 83.3)

80.0 (44.4 to 97.5)

66.7 (44.7 to 84.4)

No statistical analyses for this end point

Secondary: Phases 1 and 2: Progression-free Survival

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End point title

Phases 1 and 2: Progression-free Survival

End point description

According to RECIST 1.1, PFS was defined as the length of time from the date of the first dose study of drug until the earliest date of disease progression, as determined by investigator assessment of radiographic disease per RECIST v1.1, or death due to any cause, if it occurred sooner than progression. -9999, 9999=the upper and lower limits of the confidence interval were not estimable because too few participants had disease progression or died.

End point type

Secondary

End point timeframe

up to 1385 days

Phase 1: INCB001158 50 mg + mFOLFOX6

Phase 1: INCB001158 75 mg + mFOLFOX6

Phase 1: INCB001158 100 mg + mFOLFOX6

Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin

Phase 1: INCB001158 50 mg + Paclitaxel

Phase 1: INCB001158 75 mg + Paclitaxel

Phase 1: INCB001158 100 mg + Paclitaxel

Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: BTC (Cohort B1)

Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)

Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)

Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)

Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)

Number of subjects analysed

Units: months

median (confidence interval 95%)

3.7 (1.8 to 3.9)

6.6 (1.7 to 9999)

1.7 (1.6 to 9999)

3.9 (0.6 to 9999)

5.3 (-9999 to 9999)

6.4 (3.7 to 9999)

3.9 (0.8 to 9999)

3.7 (1.5 to 9999)

11.8 (1.7 to 16.1)

3.7 (2.8 to 9999)

8.5 (5.7 to 10.1)

7.8 (2.2 to 9999)

3.5 (1.7 to 9999)

7.1 (3.5 to 11.1)

3.7 (2.4 to 4.9)

No statistical analyses for this end point

Secondary: Cmin of INCB001158 in participants treated with INCB001158 in combination with chemotherapy on Cycle 2 Day 1 following repeated dose administration

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End point title

Cmin of INCB001158 in participants treated with INCB001158 in combination with chemotherapy on Cycle 2 Day 1 following repeated dose administration ^[22]

End point description

Cmin was defined as the minimum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

End point type

Secondary

End point timeframe

Day 1 of Cycle 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycle 2: predose; 1 and 4 hours post-dose for sparse sample collection

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 (Cohort B1)
Number of subjects analysed	7	8	8	5	13	17
Units: nanograms per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)	747 ( 35.7 )	268 ( 888 )	542 ( 102 )	1020 ( 27.2 )	633 ( 131 )	407 ( 407 )

No statistical analyses for this end point

Secondary: Cmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

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End point title

Cmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration ^[23]

End point description

Cmax was defined as the minimum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 (Cohort B1)
Number of subjects analysed	8	9	10	6	15	18
Units: ng/mL
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1	1290 ( 16.4 )	2160 ( 22.3 )	1100 ( 68.0 )	1760 ( 17.2 )	1640 ( 23.2 )	1350 ( 35.2 )
Cycle 2 Day 1	1960 ( 12.6 )	2250 ( 26.4 )	1600 ( 22.0 )	2390 ( 11.4 )	2100 ( 24.6 )	1860 ( 46.7 )

No statistical analyses for this end point

Secondary: tmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

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End point title

tmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration ^[24]

End point description

tmax was defined as the time to the maximum concentration. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 (Cohort B1)
Number of subjects analysed	8	9	10	6	15	18
Units: hours
median (full range (min-max))
Cycle 1 Day 1	4.13 (2.00 to 6.10)	4.08 (3.67 to 6.00)	5.05 (2.25 to 7.50)	4.09 (2.00 to 6.17)	3.97 (1.78 to 6.08)	4.07 (1.97 to 7.53)
Cycle 2 Day 1	4.00 (1.80 to 7.50)	4.06 (2.03 to 6.02)	4.13 (1.92 to 7.53)	3.85 (3.77 to 3.92)	3.95 (2.03 to 6.00)	4.00 (0.983 to 7.53)

No statistical analyses for this end point

Secondary: AUC0-t of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

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End point title

AUC0-t of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration ^[25]

End point description

AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 (Cohort B1)
Number of subjects analysed	8	9	10	6	15	18
Units: hours x ng/mL
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1	6910 ( 17.6 )	10600 ( 18.9 )	4680 ( 134 )	9290 ( 33.2 )	8840 ( 24.7 )	7240 ( 32.9 )
Cycle 2 Day 1	11000 ( 21.1 )	12200 ( 34.4 )	10000 ( 18.4 )	14400 ( 13.7 )	12800 ( 30.3 )	10600 ( 55.3 )

No statistical analyses for this end point

Secondary: tlast of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

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End point title

tlast of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration ^[26]

End point description

tlast was defined as the time of the last sample collected from which a concentration was measured. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1)	Ph 2: INCB001158 100 mg+Gemcitabine+Cisplatin: OC (Cohort B2)	Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1)	Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2)	Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3)	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 (Cohort B1)
Number of subjects analysed	8	9	10	6	15	18
Units: hours
median (full range (min-max))
Cycle 1 Day 1	7.53 (7.47 to 8.00)	7.53 (7.50 to 8.05)	7.50 (3.50 to 8.08)	7.53 (7.50 to 7.67)	7.65 (5.73 to 8.15)	7.73 (6.00 to 8.42)
Cycle 2 Day 1	7.50 (6.00 to 7.57)	7.60 (7.50 to 8.25)	7.57 (7.50 to 8.00)	7.55 (7.50 to 7.67)	7.58 (7.48 to 8.25)	7.58 (7.50 to 8.38)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

up to 1385 days

Adverse event reporting additional description

Treatment-emergent adverse events, defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug, have been reported.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Phase 1 and Phase 2: INCB001158 50 mg+Gemcitabine+Cisplatin

Reporting group description

Reporting group title

Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6

Reporting group description

Reporting group title

Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6

Reporting group description

Reporting group title

Phase 1 and Phase 2: INCB001158 100 mg+Gemcitabine+Cisplatin

Reporting group description

Reporting group title

Phase 1 and Phase 2: INCB001158 75 mg+Gemcitabine+Cisplatin

Reporting group description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and Day 8 of each 28-day cycle. In Phase 2, participants with BTC received intravenous gemcitabine 1000 mg/m^2 and intravenous cisplatin 25 mg/m^2 on Day 1 and 8 of each 28-day cycle, and participants with OC received intravenous gemcitabine 750 mg/m^2 and intravenous cisplatin 30 mg/m^2 on Day 1 and 8 of each 28-day cycle.

Reporting group title

Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6

Reporting group description

Reporting group title

Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel

Reporting group description

Reporting group title

Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel

Reporting group description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and with GC, EC, or OC (Phase 2) received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Reporting group title

Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel

Reporting group description

In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 mg BID starting on Day 1 of each 28-day cycle. In Phases 1 and 2, participants with advanced or metastatic solid tumors (Phase 1) and with GC, EC, or OC (Phase 2) received intravenous paclitaxel 80 mg/m^2 on Day 1, Day 8, and Day 15 of each 28-day cycle.

Reporting group title

Total

Reporting group description

Total

Serious adverse events	Phase 1 and Phase 2: INCB001158 50 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 100 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 75 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel	Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel	Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel	Total
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 7 (42.86%)	7 / 14 (50.00%)	1 / 6 (16.67%)	30 / 46 (65.22%)	1 / 4 (25.00%)	6 / 8 (75.00%)	27 / 52 (51.92%)	4 / 5 (80.00%)	4 / 7 (57.14%)	83 / 149 (55.70%)
number of deaths (all causes)	4	11	2	30	3	4	36	4	5	99
number of deaths resulting from adverse events	0	1	0	3	0	1	4	2	0	11
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
Malignant ascites
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
General disorders and administration site conditions
Device related thrombosis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	1 / 5 (20.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 2
Non-cardiac chest pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	5 / 46 (10.87%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	1 / 7 (14.29%)	9 / 149 (6.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 5	0 / 0	0 / 0	1 / 3	0 / 0	0 / 1	1 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic shock
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Female genital tract fistula
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 2	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
Pleural effusion
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	4 / 52 (7.69%)	0 / 5 (0.00%)	1 / 7 (14.29%)	5 / 149 (3.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5	0 / 0	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 2
Pneumonitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 7 (14.29%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	6 / 149 (4.03%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	1 / 2	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	2 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
Respiratory failure
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
Psychiatric disorders
Assisted suicide
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Confusional state
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood bilirubin increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular access complication
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
Supraventricular tachycardia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Brain oedema
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Haemorrhage intracranial
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 3	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	5 / 46 (10.87%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	1 / 7 (14.29%)	9 / 149 (6.04%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 5	0 / 0	0 / 1	0 / 2	0 / 0	0 / 1	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal distension
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	4 / 149 (2.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	3 / 7 (42.86%)	7 / 149 (4.70%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5	0 / 0	0 / 4	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal obstruction
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	1 / 5 (20.00%)	1 / 7 (14.29%)	3 / 149 (2.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	5 / 46 (10.87%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	7 / 149 (4.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 6	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal perforation
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	7 / 46 (15.22%)	1 / 4 (25.00%)	2 / 8 (25.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	12 / 149 (8.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 7	0 / 1	0 / 2	0 / 2	0 / 0	0 / 0	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Biliary obstruction
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic haemorrhage
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperbilirubinaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Jaundice cholestatic
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Jaundice
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Portal vein thrombosis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephritis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureteric obstruction
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection viral
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oropharyngeal candidiasis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
Septic shock
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	1 / 4 (25.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	1 / 7 (14.29%)	6 / 149 (4.03%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 3	0 / 0	0 / 2	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypernatraemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypomagnesaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	3 / 149 (2.01%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Phase 1 and Phase 2: INCB001158 50 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 100 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 75 mg+Gemcitabine+Cisplatin	Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6	Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel	Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel	Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel	Total
Total subjects affected by non serious adverse events
subjects affected / exposed	7 / 7 (100.00%)	13 / 14 (92.86%)	6 / 6 (100.00%)	45 / 46 (97.83%)	4 / 4 (100.00%)	8 / 8 (100.00%)	50 / 52 (96.15%)	5 / 5 (100.00%)	7 / 7 (100.00%)	145 / 149 (97.32%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Tumour haemorrhage
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	1	0	0	0	0	0	0	0	0	1
Tumour pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	3 / 8 (37.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	6 / 149 (4.03%)
occurrences all number	0	2	1	0	0	4	1	0	0	8
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	0 / 6 (0.00%)	4 / 46 (8.70%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	1 / 7 (14.29%)	10 / 149 (6.71%)
occurrences all number	0	2	0	4	0	0	3	0	1	10
Embolism
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	1	1	0	1	0	0	0	3
Haematoma
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	1	0	0	2
Hot flush
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	8 / 52 (15.38%)	0 / 5 (0.00%)	1 / 7 (14.29%)	9 / 149 (6.04%)
occurrences all number	0	0	0	0	0	0	12	0	1	13
Hypertension
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	4 / 52 (7.69%)	0 / 5 (0.00%)	0 / 7 (0.00%)	8 / 149 (5.37%)
occurrences all number	0	2	0	1	0	1	4	0	0	8
Hypotension
subjects affected / exposed	1 / 7 (14.29%)	2 / 14 (14.29%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	1	3	0	0	0	0	2	0	0	6
Lymphoedema
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	0	0	0	0	3	0	0	3
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	2	0	1	0	0	1	0	0	4
Catheter site erythema
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Chills
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	4 / 46 (8.70%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	8 / 149 (5.37%)
occurrences all number	0	0	0	5	0	1	5	0	0	11
Fatigue
subjects affected / exposed	1 / 7 (14.29%)	4 / 14 (28.57%)	4 / 6 (66.67%)	23 / 46 (50.00%)	1 / 4 (25.00%)	3 / 8 (37.50%)	29 / 52 (55.77%)	4 / 5 (80.00%)	2 / 7 (28.57%)	71 / 149 (47.65%)
occurrences all number	1	5	4	33	1	5	38	5	2	94
General physical health deterioration
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Influenza like illness
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	1 / 6 (16.67%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	4 / 52 (7.69%)	0 / 5 (0.00%)	0 / 7 (0.00%)	8 / 149 (5.37%)
occurrences all number	1	0	1	2	0	0	5	0	0	9
Infusion site extravasation
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	1
Localised oedema
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
Malaise
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	0	1	0	0	4	0	0	5
Mucosal inflammation
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	4 / 52 (7.69%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	0	1	0	0	4	0	0	5
Mucosal ulceration
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Oedema peripheral
subjects affected / exposed	2 / 7 (28.57%)	1 / 14 (7.14%)	0 / 6 (0.00%)	9 / 46 (19.57%)	0 / 4 (0.00%)	2 / 8 (25.00%)	13 / 52 (25.00%)	1 / 5 (20.00%)	1 / 7 (14.29%)	29 / 149 (19.46%)
occurrences all number	2	2	0	10	0	2	20	1	1	38
Oedema
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Non-cardiac chest pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	1	0	3	0	0	1	0	0	5
Pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	2 / 5 (40.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	0	2	0	0	0	2	0	4
Peripheral swelling
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	4 / 46 (8.70%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	6 / 149 (4.03%)
occurrences all number	1	0	0	5	0	0	1	0	0	7
Pyrexia
subjects affected / exposed	0 / 7 (0.00%)	3 / 14 (21.43%)	0 / 6 (0.00%)	9 / 46 (19.57%)	0 / 4 (0.00%)	3 / 8 (37.50%)	6 / 52 (11.54%)	2 / 5 (40.00%)	0 / 7 (0.00%)	23 / 149 (15.44%)
occurrences all number	0	3	0	11	0	3	8	2	0	27
Swelling
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	1	0	1	0	0	0	1	0	3
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	3 / 149 (2.01%)
occurrences all number	0	1	1	0	0	0	0	0	1	3
Reproductive system and breast disorders
Intermenstrual bleeding
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Pelvic pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	0	1	0	1	1	0	0	3
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 7 (0.00%)	3 / 14 (21.43%)	1 / 6 (16.67%)	9 / 46 (19.57%)	1 / 4 (25.00%)	3 / 8 (37.50%)	8 / 52 (15.38%)	2 / 5 (40.00%)	0 / 7 (0.00%)	27 / 149 (18.12%)
occurrences all number	0	3	2	9	1	3	10	2	0	30
Dyspnoea
subjects affected / exposed	2 / 7 (28.57%)	0 / 14 (0.00%)	0 / 6 (0.00%)	8 / 46 (17.39%)	1 / 4 (25.00%)	1 / 8 (12.50%)	7 / 52 (13.46%)	0 / 5 (0.00%)	4 / 7 (57.14%)	23 / 149 (15.44%)
occurrences all number	2	0	0	9	1	1	12	0	4	29
Dysphonia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	1	0	0	0	4	0	0	5
Dyspnoea exertional
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	0	3	1	0	0	0	0	4
Epistaxis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	4 / 52 (7.69%)	0 / 5 (0.00%)	0 / 7 (0.00%)	7 / 149 (4.70%)
occurrences all number	0	0	2	3	0	0	5	0	0	10
Hiccups
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	1	3	0	0	1	0	0	5
Hypoxia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	0	0	0	1	1	0	0	2
Oropharyngeal pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	5 / 52 (9.62%)	0 / 5 (0.00%)	1 / 7 (14.29%)	9 / 149 (6.04%)
occurrences all number	0	0	2	1	0	1	5	0	1	10
Pneumonitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	1	0	1	0	0	1	0	0	3
Pleural effusion
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	1	0	0	2
Pulmonary embolism
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	7 / 149 (4.70%)
occurrences all number	0	1	0	3	0	1	2	0	0	7
Rhinitis allergic
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	0	0	0	0	4	0	0	4
Rhinorrhoea
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	1	0	0	0	0	2	0	0	3
Wheezing
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	2	0	0	3
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	5 / 52 (9.62%)	0 / 5 (0.00%)	0 / 7 (0.00%)	7 / 149 (4.70%)
occurrences all number	0	0	0	1	0	1	6	0	0	8
Confusional state
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	1	0	0	0	0	2
Delirium
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Insomnia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	8 / 46 (17.39%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 52 (9.62%)	1 / 5 (20.00%)	0 / 7 (0.00%)	15 / 149 (10.07%)
occurrences all number	0	0	2	8	0	0	5	1	0	16
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	0	0	0	1	1	0	0	2
Alanine aminotransferase increased
subjects affected / exposed	1 / 7 (14.29%)	1 / 14 (7.14%)	0 / 6 (0.00%)	9 / 46 (19.57%)	1 / 4 (25.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	14 / 149 (9.40%)
occurrences all number	1	2	0	18	1	0	2	0	0	24
Ammonia increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	0	1	2	0	0	0	0	3
Amylase increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	2 / 8 (25.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	7 / 149 (4.70%)
occurrences all number	0	0	2	1	0	2	8	0	0	13
Aspartate aminotransferase increased
subjects affected / exposed	3 / 7 (42.86%)	1 / 14 (7.14%)	0 / 6 (0.00%)	9 / 46 (19.57%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	16 / 149 (10.74%)
occurrences all number	3	1	0	14	0	0	4	0	0	22
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 7 (14.29%)	4 / 14 (28.57%)	1 / 6 (16.67%)	3 / 46 (6.52%)	0 / 4 (0.00%)	1 / 8 (12.50%)	6 / 52 (11.54%)	0 / 5 (0.00%)	0 / 7 (0.00%)	16 / 149 (10.74%)
occurrences all number	1	4	1	4	0	1	6	0	0	17
Blood cholesterol increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	1	0	0	1	0	0	0	2
Blood magnesium decreased
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	1	0	0	0	0	1
Blood creatinine increased
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	13 / 46 (28.26%)	1 / 4 (25.00%)	2 / 8 (25.00%)	8 / 52 (15.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	26 / 149 (17.45%)
occurrences all number	0	1	1	18	1	2	9	0	0	32
Blood potassium decreased
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	1	0	0	0	0	7	0	0	8
Lipase increased
subjects affected / exposed	3 / 7 (42.86%)	2 / 14 (14.29%)	1 / 6 (16.67%)	2 / 46 (4.35%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	12 / 149 (8.05%)
occurrences all number	5	2	3	5	0	1	6	0	0	22
Neutrophil count decreased
subjects affected / exposed	4 / 7 (57.14%)	0 / 14 (0.00%)	1 / 6 (16.67%)	15 / 46 (32.61%)	0 / 4 (0.00%)	4 / 8 (50.00%)	9 / 52 (17.31%)	1 / 5 (20.00%)	0 / 7 (0.00%)	34 / 149 (22.82%)
occurrences all number	5	0	1	31	0	5	19	1	0	62
Platelet count decreased
subjects affected / exposed	5 / 7 (71.43%)	2 / 14 (14.29%)	3 / 6 (50.00%)	14 / 46 (30.43%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 52 (5.77%)	1 / 5 (20.00%)	0 / 7 (0.00%)	29 / 149 (19.46%)
occurrences all number	9	4	4	29	0	1	6	1	0	54
Weight decreased
subjects affected / exposed	0 / 7 (0.00%)	3 / 14 (21.43%)	1 / 6 (16.67%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 52 (9.62%)	0 / 5 (0.00%)	1 / 7 (14.29%)	12 / 149 (8.05%)
occurrences all number	0	3	1	2	0	0	5	0	1	12
White blood cell count decreased
subjects affected / exposed	5 / 7 (71.43%)	0 / 14 (0.00%)	1 / 6 (16.67%)	8 / 46 (17.39%)	1 / 4 (25.00%)	2 / 8 (25.00%)	11 / 52 (21.15%)	0 / 5 (0.00%)	0 / 7 (0.00%)	28 / 149 (18.79%)
occurrences all number	6	0	1	13	1	4	28	0	0	53
Weight increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	0	3	0	0	1	0	0	4
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	4 / 52 (7.69%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	0	1	0	0	4	0	0	5
Fall
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	2	0	0	0	0	2	0	0	4
Infusion related reaction
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	1	3	1	0	1	0	1	0	7
Procedural haemorrhage
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	1	0	0	2
Skin laceration
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	2	0	0	0	0	1	0	0	3
Stoma site erythema
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Wound dehiscence
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	1	0	0	2
Cardiac disorder
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	1
Palpitations
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	0	1	1	0	1	0	0	3
Supraventricular extrasystoles
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Tachycardia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	1	0	1	0	0	3	0	0	5
Nervous system disorders
Autonomic neuropathy
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Balance disorder
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Dizziness
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	1 / 6 (16.67%)	11 / 46 (23.91%)	0 / 4 (0.00%)	1 / 8 (12.50%)	10 / 52 (19.23%)	0 / 5 (0.00%)	2 / 7 (28.57%)	27 / 149 (18.12%)
occurrences all number	0	2	1	13	0	2	13	0	2	33
Dysaesthesia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	1	0	0	0	0	0	2
Dysgeusia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	3 / 46 (6.52%)	1 / 4 (25.00%)	0 / 8 (0.00%)	6 / 52 (11.54%)	0 / 5 (0.00%)	0 / 7 (0.00%)	11 / 149 (7.38%)
occurrences all number	0	0	1	3	1	0	12	0	0	17
Headache
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	1 / 6 (16.67%)	10 / 46 (21.74%)	0 / 4 (0.00%)	0 / 8 (0.00%)	9 / 52 (17.31%)	0 / 5 (0.00%)	0 / 7 (0.00%)	22 / 149 (14.77%)
occurrences all number	0	2	1	14	0	0	9	0	0	26
Hypoaesthesia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 46 (4.35%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	1	0	2	1	0	0	0	0	4
Neuropathy peripheral
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	1 / 6 (16.67%)	6 / 46 (13.04%)	0 / 4 (0.00%)	0 / 8 (0.00%)	10 / 52 (19.23%)	0 / 5 (0.00%)	3 / 7 (42.86%)	22 / 149 (14.77%)
occurrences all number	0	2	1	7	0	0	12	0	3	25
Paraesthesia
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	1 / 6 (16.67%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 52 (9.62%)	0 / 5 (0.00%)	0 / 7 (0.00%)	9 / 149 (6.04%)
occurrences all number	1	0	1	2	0	0	5	0	0	9
Peripheral sensory neuropathy
subjects affected / exposed	0 / 7 (0.00%)	4 / 14 (28.57%)	3 / 6 (50.00%)	6 / 46 (13.04%)	1 / 4 (25.00%)	0 / 8 (0.00%)	10 / 52 (19.23%)	2 / 5 (40.00%)	1 / 7 (14.29%)	27 / 149 (18.12%)
occurrences all number	0	4	4	7	1	0	11	2	1	30
Somnolence
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	1	0	0	2
Syncope
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	4 / 52 (7.69%)	0 / 5 (0.00%)	1 / 7 (14.29%)	6 / 149 (4.03%)
occurrences all number	0	2	0	0	0	0	4	0	1	7
Taste disorder
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	1	0	0	0	2	0	0	3
Tremor
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	1	0	0	0	1	0	0	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	5 / 7 (71.43%)	2 / 14 (14.29%)	2 / 6 (33.33%)	25 / 46 (54.35%)	2 / 4 (50.00%)	4 / 8 (50.00%)	21 / 52 (40.38%)	1 / 5 (20.00%)	2 / 7 (28.57%)	64 / 149 (42.95%)
occurrences all number	5	2	2	38	2	4	30	2	3	88
Leukocytosis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	0	2	0	0	4	0	0	6
Leukopenia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	1	0	0	0	0	4	0	0	5
Neutropenia
subjects affected / exposed	1 / 7 (14.29%)	5 / 14 (35.71%)	1 / 6 (16.67%)	11 / 46 (23.91%)	1 / 4 (25.00%)	2 / 8 (25.00%)	7 / 52 (13.46%)	0 / 5 (0.00%)	0 / 7 (0.00%)	28 / 149 (18.79%)
occurrences all number	1	5	1	25	1	2	17	0	0	52
Normocytic anaemia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Thrombocytopenia
subjects affected / exposed	1 / 7 (14.29%)	1 / 14 (7.14%)	1 / 6 (16.67%)	10 / 46 (21.74%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	15 / 149 (10.07%)
occurrences all number	1	1	1	16	2	0	1	0	0	22
Ear and labyrinth disorders
Deafness
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Tinnitus
subjects affected / exposed	1 / 7 (14.29%)	2 / 14 (14.29%)	0 / 6 (0.00%)	5 / 46 (10.87%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	10 / 149 (6.71%)
occurrences all number	1	2	0	5	0	0	2	0	0	10
Eye disorders
Foreign body sensation in eyes
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Glaucoma
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Retinopathy
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	1	0	0	0	0	1
Vision blurred
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	0	3	0	0	1	0	0	4
Vitreous floaters
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	1	2	0	0	1	0	0	4
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	1	2	0	0	2	0	0	5
Abdominal distension
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	5 / 46 (10.87%)	0 / 4 (0.00%)	0 / 8 (0.00%)	8 / 52 (15.38%)	0 / 5 (0.00%)	1 / 7 (14.29%)	14 / 149 (9.40%)
occurrences all number	0	0	0	5	0	0	11	0	1	17
Abdominal pain
subjects affected / exposed	1 / 7 (14.29%)	5 / 14 (35.71%)	1 / 6 (16.67%)	9 / 46 (19.57%)	1 / 4 (25.00%)	2 / 8 (25.00%)	15 / 52 (28.85%)	0 / 5 (0.00%)	1 / 7 (14.29%)	35 / 149 (23.49%)
occurrences all number	1	7	1	18	1	2	19	0	1	50
Abdominal pain lower
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	0	2	0	0	3	0	0	5
Abdominal pain upper
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	1 / 6 (16.67%)	4 / 46 (8.70%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 52 (9.62%)	0 / 5 (0.00%)	0 / 7 (0.00%)	12 / 149 (8.05%)
occurrences all number	0	2	1	4	0	0	8	0	0	15
Ascites
subjects affected / exposed	3 / 7 (42.86%)	0 / 14 (0.00%)	0 / 6 (0.00%)	4 / 46 (8.70%)	0 / 4 (0.00%)	1 / 8 (12.50%)	4 / 52 (7.69%)	0 / 5 (0.00%)	1 / 7 (14.29%)	13 / 149 (8.72%)
occurrences all number	3	0	0	5	0	1	7	0	2	18
Cheilitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	4 / 52 (7.69%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	0	0	0	0	4	0	0	4
Constipation
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	1 / 6 (16.67%)	19 / 46 (41.30%)	2 / 4 (50.00%)	2 / 8 (25.00%)	13 / 52 (25.00%)	1 / 5 (20.00%)	1 / 7 (14.29%)	41 / 149 (27.52%)
occurrences all number	0	2	3	29	2	2	13	1	1	53
Diarrhoea
subjects affected / exposed	2 / 7 (28.57%)	6 / 14 (42.86%)	3 / 6 (50.00%)	11 / 46 (23.91%)	0 / 4 (0.00%)	3 / 8 (37.50%)	16 / 52 (30.77%)	1 / 5 (20.00%)	3 / 7 (42.86%)	45 / 149 (30.20%)
occurrences all number	4	7	4	17	0	6	25	1	3	67
Dry mouth
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	1 / 7 (14.29%)	4 / 149 (2.68%)
occurrences all number	0	0	0	0	1	1	1	0	1	4
Dyspepsia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	5 / 46 (10.87%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	1 / 7 (14.29%)	9 / 149 (6.04%)
occurrences all number	0	0	1	6	0	0	2	0	1	10
Dysphagia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	0	1	0	1	3	0	0	5
Faeces soft
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Gastrointestinal disorder
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	2	0	0	0	2
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	1 / 4 (25.00%)	1 / 8 (12.50%)	4 / 52 (7.69%)	0 / 5 (0.00%)	0 / 7 (0.00%)	9 / 149 (6.04%)
occurrences all number	0	0	0	3	1	1	4	0	0	9
Glossodynia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	1
Haemorrhoids
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	1	0	3	0	0	0	0	0	4
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Nausea
subjects affected / exposed	1 / 7 (14.29%)	5 / 14 (35.71%)	3 / 6 (50.00%)	25 / 46 (54.35%)	1 / 4 (25.00%)	5 / 8 (62.50%)	21 / 52 (40.38%)	3 / 5 (60.00%)	3 / 7 (42.86%)	67 / 149 (44.97%)
occurrences all number	1	5	6	44	1	7	43	3	4	114
Oesophagitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Proctalgia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	1	0	0	0	0	0	2
Rectal haemorrhage
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	1 / 7 (14.29%)	2 / 149 (1.34%)
occurrences all number	0	0	0	0	0	0	1	0	1	2
Retching
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Stomatitis
subjects affected / exposed	0 / 7 (0.00%)	3 / 14 (21.43%)	2 / 6 (33.33%)	6 / 46 (13.04%)	0 / 4 (0.00%)	0 / 8 (0.00%)	10 / 52 (19.23%)	0 / 5 (0.00%)	0 / 7 (0.00%)	21 / 149 (14.09%)
occurrences all number	0	3	2	6	0	0	12	0	0	23
Vomiting
subjects affected / exposed	1 / 7 (14.29%)	3 / 14 (21.43%)	1 / 6 (16.67%)	14 / 46 (30.43%)	1 / 4 (25.00%)	3 / 8 (37.50%)	18 / 52 (34.62%)	3 / 5 (60.00%)	1 / 7 (14.29%)	45 / 149 (30.20%)
occurrences all number	1	3	1	26	1	3	29	6	2	72
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	1 / 4 (25.00%)	0 / 8 (0.00%)	18 / 52 (34.62%)	2 / 5 (40.00%)	1 / 7 (14.29%)	24 / 149 (16.11%)
occurrences all number	0	0	0	2	1	0	20	2	1	26
Dermatitis acneiform
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Drug eruption
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Dry skin
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	1	0	0	0	0	3	0	0	4
Hyperhidrosis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	1 / 7 (14.29%)	4 / 149 (2.68%)
occurrences all number	0	1	0	0	0	0	5	0	1	7
Nail disorder
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 52 (9.62%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	0	0	0	0	6	0	0	6
Photosensitivity reaction
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Pruritus
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	6 / 52 (11.54%)	1 / 5 (20.00%)	0 / 7 (0.00%)	10 / 149 (6.71%)
occurrences all number	0	0	0	5	0	0	8	1	0	14
Rash maculo-papular
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	2 / 46 (4.35%)	2 / 4 (50.00%)	0 / 8 (0.00%)	6 / 52 (11.54%)	0 / 5 (0.00%)	1 / 7 (14.29%)	12 / 149 (8.05%)
occurrences all number	0	0	2	2	2	0	9	0	1	16
Rash
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	5 / 46 (10.87%)	0 / 4 (0.00%)	0 / 8 (0.00%)	7 / 52 (13.46%)	1 / 5 (20.00%)	0 / 7 (0.00%)	14 / 149 (9.40%)
occurrences all number	0	1	0	5	0	0	7	1	0	14
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	0	2	0	1	2	0	0	5
Dysuria
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	0	0	2	0	0	4	0	0	6
Haematuria
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	1	0	0	1	0	1	3	0	0	6
Proteinuria
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Renal failure
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	2	0	0	0	0	2
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	0	0	2	0	1	0	0	3
Hypothyroidism
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	6 / 52 (11.54%)	0 / 5 (0.00%)	0 / 7 (0.00%)	6 / 149 (4.03%)
occurrences all number	0	0	0	0	0	0	7	0	0	7
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 7 (28.57%)	2 / 14 (14.29%)	0 / 6 (0.00%)	8 / 46 (17.39%)	0 / 4 (0.00%)	0 / 8 (0.00%)	11 / 52 (21.15%)	1 / 5 (20.00%)	0 / 7 (0.00%)	24 / 149 (16.11%)
occurrences all number	2	2	0	10	0	0	13	1	0	28
Back pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	2 / 6 (33.33%)	9 / 46 (19.57%)	0 / 4 (0.00%)	3 / 8 (37.50%)	9 / 52 (17.31%)	0 / 5 (0.00%)	1 / 7 (14.29%)	25 / 149 (16.78%)
occurrences all number	0	2	2	14	0	4	10	0	1	33
Groin pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	1	0	0	2
Limb discomfort
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	2 / 149 (1.34%)
occurrences all number	0	0	0	1	0	0	0	0	1	2
Myalgia
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	2 / 8 (25.00%)	7 / 52 (13.46%)	0 / 5 (0.00%)	0 / 7 (0.00%)	12 / 149 (8.05%)
occurrences all number	1	0	1	1	0	2	9	0	0	14
Muscular weakness
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	6 / 149 (4.03%)
occurrences all number	0	0	0	3	0	1	6	0	0	10
Muscle spasms
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	7 / 46 (15.22%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 52 (9.62%)	0 / 5 (0.00%)	1 / 7 (14.29%)	14 / 149 (9.40%)
occurrences all number	0	0	1	9	0	0	6	0	1	17
Neck pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	1 / 5 (20.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	1	0	1	0	0	1	2	0	5
Osteonecrosis of jaw
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	1	0	0	0	0	1
Pain in extremity
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	1 / 8 (12.50%)	4 / 52 (7.69%)	2 / 5 (40.00%)	0 / 7 (0.00%)	10 / 149 (6.71%)
occurrences all number	0	0	0	3	0	1	4	2	0	10
Sacral pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Infections and infestations
Biliary tract infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
Cellulitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	0	0	0	3	0	0	1	0	0	4
Conjunctivitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Ear infection
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	1	0	0	0	0	0	0	0	0	1
Enterocolitis infectious
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Gastroenteritis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Herpes zoster
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	1	0	0	0	0	0	0	0	0	1
Infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	0	0	0	2	0	0	0	2
Lip infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	0	1	0	0	0	0	0	0	1
Lower respiratory tract infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	1 / 7 (14.29%)	5 / 149 (3.36%)
occurrences all number	0	1	0	3	0	0	1	0	1	6
Oral herpes
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	0	0	0	0	0	0	3	0	0	3
Oral candidiasis
subjects affected / exposed	1 / 7 (14.29%)	2 / 14 (14.29%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	1	2	0	0	0	0	0	0	0	3
Peritonitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	0	0	0	1	1	0	0	2
Rhinitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	1 / 5 (20.00%)	0 / 7 (0.00%)	5 / 149 (3.36%)
occurrences all number	0	1	1	1	0	0	1	1	0	5
Skin infection
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	4 / 149 (2.68%)
occurrences all number	1	0	0	1	0	0	2	0	0	4
Upper respiratory tract infection
subjects affected / exposed	1 / 7 (14.29%)	2 / 14 (14.29%)	1 / 6 (16.67%)	5 / 46 (10.87%)	0 / 4 (0.00%)	0 / 8 (0.00%)	7 / 52 (13.46%)	0 / 5 (0.00%)	1 / 7 (14.29%)	17 / 149 (11.41%)
occurrences all number	1	3	1	5	0	0	9	0	1	20
Urinary tract infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	6 / 46 (13.04%)	0 / 4 (0.00%)	0 / 8 (0.00%)	6 / 52 (11.54%)	0 / 5 (0.00%)	1 / 7 (14.29%)	13 / 149 (8.72%)
occurrences all number	0	0	0	7	0	0	15	0	1	23
Viral upper respiratory tract infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	1	0	0	0	0	0	2
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 7 (28.57%)	4 / 14 (28.57%)	2 / 6 (33.33%)	12 / 46 (26.09%)	1 / 4 (25.00%)	3 / 8 (37.50%)	10 / 52 (19.23%)	1 / 5 (20.00%)	2 / 7 (28.57%)	37 / 149 (24.83%)
occurrences all number	2	4	2	14	1	3	16	1	2	45
Dehydration
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	1 / 8 (12.50%)	9 / 52 (17.31%)	0 / 5 (0.00%)	0 / 7 (0.00%)	14 / 149 (9.40%)
occurrences all number	0	2	0	4	0	2	10	0	0	18
Food intolerance
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Hypercholesterolaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	0	1	0	0	0	1	0	0	2
Hypercalcaemia
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 149 (0.67%)
occurrences all number	1	0	0	0	0	0	0	0	0	1
Hyperglycaemia
subjects affected / exposed	3 / 7 (42.86%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	2 / 8 (25.00%)	5 / 52 (9.62%)	0 / 5 (0.00%)	0 / 7 (0.00%)	13 / 149 (8.72%)
occurrences all number	4	1	0	3	0	7	8	0	0	23
Hypernatraemia
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	1	0	0	0	0	0	1	0	0	2
Hyperkalaemia
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	1 / 6 (16.67%)	3 / 46 (6.52%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 52 (5.77%)	0 / 5 (0.00%)	1 / 7 (14.29%)	9 / 149 (6.04%)
occurrences all number	1	0	1	3	0	0	5	0	1	11
Hypertriglyceridaemia
subjects affected / exposed	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 46 (2.17%)	0 / 4 (0.00%)	2 / 8 (25.00%)	2 / 52 (3.85%)	0 / 5 (0.00%)	0 / 7 (0.00%)	6 / 149 (4.03%)
occurrences all number	2	0	0	1	0	3	3	0	0	9
Hyperuricaemia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	6 / 149 (4.03%)
occurrences all number	0	1	0	3	0	1	1	0	0	6
Hypoalbuminaemia
subjects affected / exposed	1 / 7 (14.29%)	1 / 14 (7.14%)	1 / 6 (16.67%)	5 / 46 (10.87%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 52 (5.77%)	0 / 5 (0.00%)	2 / 7 (28.57%)	14 / 149 (9.40%)
occurrences all number	3	1	2	5	0	2	3	0	2	18
Hypocalcaemia
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	7 / 46 (15.22%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 52 (3.85%)	0 / 5 (0.00%)	2 / 7 (28.57%)	13 / 149 (8.72%)
occurrences all number	0	1	0	7	0	2	2	0	3	15
Hypoglycaemia
subjects affected / exposed	1 / 7 (14.29%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 52 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	3 / 149 (2.01%)
occurrences all number	1	1	0	0	0	1	0	0	0	3
Hypokalaemia
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	0 / 6 (0.00%)	3 / 46 (6.52%)	0 / 4 (0.00%)	1 / 8 (12.50%)	8 / 52 (15.38%)	0 / 5 (0.00%)	1 / 7 (14.29%)	15 / 149 (10.07%)
occurrences all number	0	3	0	3	0	2	12	0	2	22
Hypomagnesaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	6 / 46 (13.04%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 52 (5.77%)	0 / 5 (0.00%)	1 / 7 (14.29%)	11 / 149 (7.38%)
occurrences all number	0	0	0	6	0	1	3	0	1	11
Hyponatraemia
subjects affected / exposed	0 / 7 (0.00%)	2 / 14 (14.29%)	1 / 6 (16.67%)	5 / 46 (10.87%)	1 / 4 (25.00%)	1 / 8 (12.50%)	5 / 52 (9.62%)	0 / 5 (0.00%)	1 / 7 (14.29%)	16 / 149 (10.74%)
occurrences all number	0	3	1	8	1	1	9	0	2	25
Hypophosphataemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	2 / 46 (4.35%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 52 (9.62%)	0 / 5 (0.00%)	0 / 7 (0.00%)	7 / 149 (4.70%)
occurrences all number	0	0	0	2	0	0	5	0	0	7
Vitamin D deficiency
subjects affected / exposed	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 46 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 52 (1.92%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 149 (1.34%)
occurrences all number	0	1	0	0	0	0	1	0	0	2

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Were there any global substantial amendments to the protocol? Yes

31 Oct 2017

The primary purpose of this amendment was to address changes requested by the Medicines & Healthcare products Regulatory Agency (MHRA) in the United Kingdom.

27 Sep 2018

The primary purpose of this amendment was to update the inclusion criteria for the microsatellite stable colorectal cancer (MSS-CRC) expansion cohort.

17 May 2019

The primary purpose of this amendment was to change the study drug formulation.

09 Dec 2020

The primary purpose of this amendment was to provide guidance for the management of ongoing participants, as enrollment was complete and sufficient data had been collected for primary and secondary endpoint analysis.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of INCB001158 in Combination With Chemotherapy, in Subjects With Advanced or Metastatic Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phases 1 and 2: Number of participants with any treatment-emergent adverse event (TEAE)

Primary: Phases 1 and 2: Number of participants with any treatment-emergent adverse event (TEAE)

Primary: Phase 1: Number of participants with any dose-limiting toxicity (DLT)

Primary: Phase 1: Number of participants with any dose-limiting toxicity (DLT)

Primary: Recommended Phase 2 dose (RP2D) of INCB001158 when given in combination with each chemotherapy regimen

Primary: Recommended Phase 2 dose (RP2D) of INCB001158 when given in combination with each chemotherapy regimen

Primary: Phase 2: Objective Response Rate (ORR)

Primary: Phase 2: Objective Response Rate (ORR)

Secondary: Phase 1: ORR

Secondary: Phase 1: ORR

Secondary: Phases 1 and 2: Duration of Response

Secondary: Phases 1 and 2: Duration of Response

Secondary: Phases 1 and 2: Disease Control Rate

Secondary: Phases 1 and 2: Disease Control Rate

Secondary: Phases 1 and 2: Progression-free Survival

Secondary: Phases 1 and 2: Progression-free Survival

Secondary: Cmin of INCB001158 in participants treated with INCB001158 in combination with chemotherapy on Cycle 2 Day 1 following repeated dose administration

Secondary: Cmin of INCB001158 in participants treated with INCB001158 in combination with chemotherapy on Cycle 2 Day 1 following repeated dose administration

Secondary: Cmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Secondary: Cmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Secondary: tmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Secondary: tmax of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Secondary: AUC0-t of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Secondary: AUC0-t of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Secondary: tlast of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Secondary: tlast of INCB001158 in participants treated with INCB001158 in combination with chemotherapy following the first dose on Cycle 1 Day 1 and on Cycle 2 Day 1 following repeated dose administration

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of INCB001158 in Combination With Chemotherapy, in Subjects With Advanced or Metastatic Solid Tumors